Imatinib treatment for Multiple Sclerosis (MS) Relapses

• Register: EUCTR
• Last refreshed on: 3 September 2018
• Main ID: EUCTR2018-000620-34-SE
• Date of registration: 14/03/2018
• Prospective Registration: Yes
• Primary sponsor: Department of Clinical Neuroscience, Karolinska Institutet
• Public title: Imatinib treatment for Multiple Sclerosis (MS) Relapses
• Scientific title: Imatinib for Multiple Sclerosis (MS) Relapses - a Phase II, Randomised Study - Imatinib MS
• Date of first enrolment: 24/04/2018
• Target sample size: 200
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000620-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden

Contacts

• Name: CMM:04
• Affiliation: Karolinska Institutet

• Name: CMM:04
• Affiliation: Karolinska Institutet

Key inclusion & exclusion criteria

Inclusion criteria:
1. An acute exacerbation, relapse, in persons with RRMS, either newly diagnosis or on treatment with one of the long-term immunomodulatory drugs, or possible MS where the diagnosis is supported by typical MRI or cerebrospinal fluid changes typical of MS (this enables inclusion of persons with a first neuroinflammatory bout, with high risk of developing MS before fulfilling the McDonald criteria for definite MS, or high risk for developing MS in the category clinically isolated syndrome (CIS)/possible MS with supporting MRI lesions and/or cerebrospinal fluid abberations suggesting intra-thecal immunoglobulin synthesis with oligoclonal bands/and/or increased free Kappa Light chains. The relapse should be deemed to require relapse treatment by the investigator and affect a functional domain with a minimum of grade 2.
2. 18-55 years of age
3. Affection of any of the following EDSS sub-domains representing the targeted neurological deficit: 1. Visual function. grade 0-6, 2. Brain stem function grade 0-5. 3. Pyramidal function, grade 0-6. 4. Cerebellar function, grade 0-5. 5. Sensory function grade 0-6, and deterioration at least one step in any of these EDSS domains
4. EDSS = 6 before the acute exacerbation
5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using effective methods of contraception during the study. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly according to CTFG, September 2014 “Recommendations related to contraception and pregnancy testing in clinical trials”. Such methods include:
a. Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation.
-oral
-intravaginal
-transdermal
b. progestogen-only hormonal contraception associated with inhibition of ovulation
- oral
- injectable
- implantable
c. intrauterine device (IUD)
d. intrauterine hormone-releasing system (IUS)
e. bilateral tubal occlusion
f. total abstinence or vasectomized partner.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. A peudo-relapse should be excluded, as deemed by the experienced treating neurologist, and as evidenced by an active infection, likely with fever, with reappearing new signs and symptoms in a previously affected neurological function.
2. Inability to provide informed consent
3. Concomitant medication with drugs which may increase the plasma concentration of Imatinib - ketokonazol, itrakonazol, erythromycin and claritomycin
4. Concomitant medication with drugs which may decrease the plasma concentration of Imatinib: Dexametason, phenytoin, carbamazepin, rifampicin, phenobarbital, fosphenytoin, primidon, Hypericum perforatum (Johannesört, St John's wort).
5. Female patients with childbearing potential, if pregnancy cannot be excluded by pregnancy test (urine point-of-care pregnancy test).
6. Patient is participating in other interventional study
7. General infection or any other condition judged by the treating neurologist to contra-indicate Imatinib
8. Any laboratory deviation of general bodily functions such as kidney, or renal function judged to be of clinical significance by the treating neurologist constitutes an exclusion criteria.
9. Patients with a positive Hepatitis B-DNA test result or serology indicating latent infection.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with clinically definite Multiple Sclerosis (MS) according to the McDonald Criteria, or possible MS (also named clinically isolated syndrome-CIS, as a first manifestation of MS, where there are radiological and/or cerebrospinal fluid signs consistent with MS), which display an acute relapse
MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: LLT Classification code 10028247 Term: Multiple sclerosis like syndrome System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IMATINIB MESILATE
CAS Number: 220127-57-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Solu-Medrol
Product Name: Solu-Medrol
Pharmaceutical Form: Injection
INN or Proposed INN: Methylprednisolone
Other descriptive name: METHYLPREDNISOLONE SODIUM SUCCINATE
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Secondary Objective: 1.To investigate Imatinib versus MP with regard to worsening of FSS
2.To investigate Imatinib versus MP with regard to change of EDSS
3.To investigate Imatinib versus MP with regard to change in 9-hole peg test
4.To investigate Imatinib versus MP with regard to change in timed 25-foot walk
5.To investigate Imatinib versus MP with regard to change in SDMT
6.To investigate Imatinib versus MP with regard to change Multiple Sclerosis Impact Scale (MSIS-29; MS-specific QoL scale)
7.To investigate Imatinib versus MP with regard to mean change in EQ5D
8.To investigate Imatinib versus MP with regards to new brain MRI lesions

Primary end point(s): 1. The primary endpoint is mean change between baseline and day 28 in the most worsened FSS due to the acute relapse comparing MP and Imatinib. In case more than one domain is affected, priority of selected FSS should be in the following order: 1) Pyramidal, 2) Brain stem, 3) Cerebellar, 4) Visual, 5) Sensory. At least a two step deterioration due to neuroinflammatory bout should have occurred. Bowel and Cerebral domains will not be considered in the primary endpoints.

Main Objective: To investigate if treatment with Imatinib results in a better outcome than standard care in form of Methylprednisolone(MP) after MS-associated relapses.

Timepoint(s) of evaluation of this end point: 28 days

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 28 days

Secondary end point(s): 1.Mean change between baseline and week 12 in the most worsened FSS due to the acute relapse
2.Mean EDSS change between baseline and day 28
3.Mean change in 9-hole peg test (evaluates upper limb function) between baseline and day 28.
4.Mean change in timed 25- walk between baseline and day 28.
5.Mean change in SDMT (evaluates cognitive function) between baseline and day 28.
6.Mean change in Multiple Sclerosis Impact Scale (MSIS-29; MS-specific QoL scale) between baseline and day 28.
7.Mean change in EQ5D (general QoL) between baseline and day 28.
8.Any difference in number of new brain MRI lesions at day 14 and day 28 with regards to the baseline, comparing the two drugs.

Secondary ID(s)

Imatinib-MS

Source(s) of Monetary Support

Vetenskapsrådet